Pima Indians have a high prevalence of obesity, diabetes mellitus and hyperinsulipemia, but they have low plasma cholesterol levels, reduced low density lipoprotein (LDL) synthesis, and decreased incidence of cardiovascular disease. Lipoprotein metabolism in Pima Indians is being investigated in order to further understand control of lipoprotein metabolism in this population and how lipid metabolism is influenced by obesity and diabetes. Simultaneous studies have been performed of very low density lipoprotein (VLDL) apoB and LDL apoB metabolism using a double isotope procedure. Methods have been developed to facilitate isolation apoB and estimation of plasma volume. Preliminary studies in a group of male Pimas indicated a larger proportion of VLDL is metabolized without conversion to LDL; this alternate pathway might be a mechanism for maintenance of low LDL in this population. VLDL and LDL apoB metabolism were examined in a group of 14 subjects over wide range of obesity. Obesity results in a greatly increased flux of VLDL apoB. LDL apoB levels were not elevated in the obese subjects, because of both increased metabolism of VLDL through the alternate pathway and increased catabolism of LDL. Free fatty acid turnover studies were also conducted in a group of Pimas of varying body weights. Obesity was associated with increased flux of free fatty acids without increasing plasma concentrations. This could account for the increased VLDL production in these individuals. The results of lipoprotein metabolic studies in Pimas to date suggest a large flux of substrates and regulators (i.e. insulin) which cause overproduction of lipoproteins, but that compensatory mechanisms are operative which result in maintenance of low plasma concentrations.